Developing a fundamental understanding of the interactions of chemical warfare agents (CWAs) with surfaces is essential for the rational design of new sorbents, sensors, and decontamination strategies. The interactions of chemical warfare agent simulants, molecules which retain many of the same chemical or physical properties of the agent without the toxic effects, with amorphous silica were conducted to investigate how small changes in chemical structure affect the overall chemistry. Experiments investigating the surface chemistry of two classes of CWAs, nerve and blister agents, were performed in ultrahigh vacuum to provide a well-characterized system in the absence of background gases. Transmission infrared spectroscopy and temperature-programmed desorption techniques were used to learn about the adsorption mechanism and to measure the activation energy for desorption for each of the simulant studied. In the organophosphate series, the simulants diisopropyl methylphosphonate (DIMP), dimethyl methylphosphonate (DMMP), trimethyl phosphate (TMP), dimethyl chlorophosphate (DMCP), and methyl dichlorophosphate (MDCP) were all observed to interact with the silica surface through the formation of a hydrogen bond between the phosphoryl oxygen of the simulant and an isolated hydroxyl group on the surface. In the limit of zero coverage, and after defect effects were excluded, the activation energies for desorption were measured to be 57.9 ± 1, 54.5 ± 0.3, 52.4 ± 0.6, 48.4 ± 1, and 43.0 ± 0.8 kJ/mol for DIMP. DMMP, TMP, DMCP, and MDCP respectively. The adsorption strength was linearly correlated to the magnitude of the frequency shift of the ν(SiO-H) mode upon simulant adsorption. The interaction strength was also linearly correlated to the calculated negative charge on the phosphoryl oxygen, which is affected by the combined inductive effects of the simulants’ different substituents. From the structure-function relationship provided by the simulant studies, the CWA, Sarin is predicted to adsorb to isolated hydroxyl groups of the silica surface via the phosphoryl oxygen with a strength of 53 kJ/mol. The interactions of two common mustard simulants, 2-chloroethyl ethyl sulfide (2-CEES) and methyl salicylate (MeS), with amorphous silica were also studied. 2-CEES was observed to adsorb to form two different types of hydrogen bonds with isolated hydroxyl groups, one via the S moiety and another via the Cl moiety. The desorption energy depends strongly on the simulant coverage, suggesting that each 2-CEES adsorbate forms two hydrogen bonds. MeS interacts with the surface via a single hydrogen bond through either its hydroxyl or carbonyl functionality. While the simulant work has allowed us to make predictions agent-surface interactions, actual experiments with the live agents need to be conducted to fully understand this chemistry. To this end, a new surface science instrument specifically designed for agent-surface experiments has been developed, constructed, and tested. The instrument, located at Edgewood Chemical Biological Center, now makes it possible to make direct comparisons between simulants and agents that will aid in choosing which simulants best model live agent chemistry for a given system. These fundamental studies will also contribute to the development of new agent detection and decontamination strategies. / Ph. D.

Anionic polymerization and controlled radical polymerization enabled the synthesis of novel block copolymers with non-covalent interactions (electrostatic interaction and/or hydrogen bonding) to examine the relationships between mesoscale phenomenon and macroscopic physical properties. Non-covalent interactions offer extra intra- and inter-molecular interactions to achieve stimuli-responsive materials in various applications, such as artificial muscles, thermoplastic elastomers, and reversible biomacromolecule binding. The relationship between non-covalent interaction promoted mesoscale phenomenon (such as morphology) and consequent macroscopic physical properties is the key to optimize material design and improve end-use performance for emerging applications. Pendant hydrogen bonding in ABA block copolymers promoted microphase separation and delayed the order-disorder transition, resulting in tunable morphologies (through composition changes) and extended rubbery plateaus. Reversible addition-fragmentation chain transfer (RAFT) polymerization afforded a facile synthesis of ABA triblock copolymers with hydrogen bonding (urea sites) and electrostatic interactions (pyridinium groups). Pyridine groups facilitated hydrogen bonding through a preorganization effect, leading to highly ordered, long-range lamellar morphology and a significant increase of flow temperature (Tf) 80 °C above the hard block Tg. After quaternization of pyridine groups, electrostatic interaction, as a second physical crosslinking mechanism, disrupted ordered lamellar morphology and decreased Tf. Yet, extra physical crosslinking from electrostatic interactions pertained ordered hydrogen bonding at high temperature and exhibited improved stress-relaxation properties. Both conventional free radical polymerization and RAFT polymerization generated a library of poly(ionic liquid) (PIL) homopolymers with imidazolium groups as bond charge moieties. A long chain alkyl spacer between imidazolium groups and the polymer backbones ensured a low glass transition temperature (Tg), which is beneficial to ion conductivity. Four different counter anions enabled readily tunable Tgs all below room temperature and showed promising ion conductivities as high as 2.45 × 10⁻⁵ S/cm at 30 °C. For the first time, the influence of counter anions on radical polymerization kinetics was observed and investigated thoroughly using in situ FTIR, NMR diffusometry, and simulation. Monomer diffusion and aggregation barely contributed to the kinetic differences, and the Marcus theory was applied to explain the polymerization kinetic differences which showed promising simulation results. RAFT polymerization readily prepared AB diblock, ABA triblock and (AB)3 3-arm diblock copolymers using the ionic liquid (IL) monomers discussed above and deuterated/hydrogenated styrene. We demonstrated the first example of in situ morphology studies during an actuation process, and counter anions with varied electrostatic interactions showed different mesoscale mechanisms, which accounted for macroscopic actuation. The long chain alkyl spacer between imidazolium groups and polymer backbones decoupled ion dynamics and structural relaxation. For the first time, composition changes of block copolymers achieved tunable viscoelastic properties without altering ion conductivity, which provided an ideal example for actuation materials, solid electrolytes, and ion exchange membranes. / Ph. D. / My research focuses on the synthesis of novel soft materials with a special interest in responsive polymers. The incorporation of responsive chemistry, such as hydrogen bonding and ionic interactions, enables soft materials with complex responsive behavior were achieved. Polymers with ion pairs promise great potential as solid-state electrolytes (which transfer ions to generate current) to eliminate potential fire hazard in batteries, which has been an arising concern for modern cellphone and electric car industry. The introduction of strong dipoles into polymers allows the fabrication of actuators, which convert electric signals to physical movement. Under applied voltage, polymers bend within seconds while holding physical loads. Actuator studies in polymers paves the way towards artificial muscles as well as soft robotics. Temperature responsive hydrogen bonding in polymers offers drastically different viscoelastic properties at different temperature and serves as the key mechanism in holt-melt adhesives, controlled drug release, and high performance materials.

The dynamic characteristics of hydrogen and ionic bonding contributes to the reversible properties of acrylic polymers, opening new avenues for designing materials with mechanical strength and processability. These non-covalent interactions function as physical crosslinks, which provide enhanced structural and mechanical integrity to acrylic block copolymers. The strong hydrogen bonding or ionic interaction also directs self-assembly to hierarchical microstructures, which enables many applications including thermoplastic elastomers and energy storage devices. Inspired by complementary hydrogen bonding interactions between nucleobase pairs in DNA, a series of bioinspired nucleobase-acrylate monomers such as adenine acrylate (AdA), thymine acrylate (ThA), cytosine acrylate (CyA) were designed, whose synthesis were afforded by aza-Michael addition. Among those nucleobases, cytosine arises as a unique category. It is not only able to self-associate via weak hydrogen bonds, but also forms quadruple hydrogen-bond bearing units (ureido-cytosine) when functionalized with isocyanates. Reversible addition-fragmentation chain transfer polymerization (RAFT) yielded acrylic ABA triblock copolymers with CyA external hard blocks. A subsequent post-functionalization using hexyl-isocyanate generated the corresponding ureido-cytosine acrylate(UCyA)-containing triblock copolymers. The self-complementary quadruple hydrogen bonding in the UCyA polymers achieved a broader service temperature window, while the alkyl chain ends of UCyA units allowed tunability of the mechanical strength to apply as thermoplastic elastomers. In addition, quadruple hydrogen bonding induced stronger propensity of self-assembly and denser packing of the polymers, which contributed to a well-defined ordered morphology and enhanced resistance to moisture uptake. A facile 2-step synthesis provided doubly-charged styrenic DABCO salt monomer(VBDC₁₈BrCl) containing an octadecyl tail. RAFT polymerization allowed the preparation of DABCO ABA block copolymers with defined molecular weights and low polydispersity. Thermal analysis revealed a melting transition of the VBDC₁₈BrCl block copolymer resulting from the side-chain crystallization of the long alkyl tail. Systematic mechanical comparisons between DABCO salt-containing copolymers and the corresponding singly-charged polymer controls demonstrated superior mechanical properties attributable to a stronger ionic interaction between the doubly-charged groups. Morphological characterizations revealed a well-ordered lamellar microstructure and a unique three-phase morphology of the DABCO block copolymers, which involve a soft phase, a hard phase, and an ionic aggregates domain dispersed within the hard domain. / Master of Science

Yes / Investigations of structural reactivity, molecular interactions and vibrational characterization of pharmaceutical drugs are helpful in understanding their behaviour. The aim of this study is to determine the molecular, electronic and chemical properties of the antibiotic drug nitrofurantoin (NF), after cocrystallisation with 3-aminobenzoic acid (3ABA) and to understand how those changes lead to variation of properties in the cocrystal NF–3ABA. NF–3ABA formation is explained by stabilization via the hydrogen-bond network between NF and 3ABA molecules. It is thoroughly characterized by IR, Raman and CP-MAS solid-state 13C NMR techniques, along with quantum chemical calculations. The results of IR, Raman, and 13C NMR analyses showed that imide N–H23 and C12[double bond, length as m-dash]O of NF interact with the acid C[double bond, length as m-dash]O and –OH groups in 3-ABA, respectively. Therefore the IR, Raman, and 13C NMR spectra verified the formation of N–H⋯O and O–H⋯O hydrogen bonds. To study hydrogen bonding interactions theoretically in NF–3ABA, two functionals B3LYP and wB97X-D have been used. A comparison is made between the results obtained by B3LYP and those predicted at the wB97X-D level. It is found that wB97X-D is best applied density functional theory (DFT) functional to describe the hydrogen bonding interactions. The strength and nature of hydrogen bonding in NF–3ABA have been analysed by quantum theory of atoms in molecules (QTAIM) and natural bond orbital (NBO) analysis. To validate the results obtained by QTAIM theory and to study the long-range forces, such as van der Waals interactions, the steric effects in NF–3ABA, the reduced density gradient (RDG) and the isosurface have been plotted using Multiwfn software. QTAIM and isosurface analysis suggested that the hydrogen bonding interactions present in NF–3ABA are moderate in nature. The calculated HOMO–LUMO energy gap shows that NF–3ABA is more active than NF and 3ABA. Chemical reactivity descriptors are calculated to understand the various aspects of pharmacological sciences. Chemical reactivity parameters show that NF–3ABA is softer and chemically more reactive than NF. The results suggest that cocrystals can be a feasible alternative for positively changing the targeted physicochemical properties of an active pharmaceutical ingredient (API). / V. R. Vangala acknowledges the financial support of the Royal Society of Chemistry for mobility grant (2015/17).

Yes / Pharmaceutical salt, nitrofurantoin–4-dimethylaminopyridine (NF-DMAP), along with its native components NF and DMAP are scrutinized by FT-IR and FT-Raman spectroscopy along with density functional theory so that an insight into the H-bond patterns in the respective crystalline lattices can be gained. Two different functionals, B3LYP and wB97X-D, have been used to compare the theoretical results. The FT-IR spectra obtained for NF-DMAP and NF clearly validate the presence of C33–H34⋅⋅⋅O4 and N23–H24⋅⋅⋅N9 hydrogen bonds by shifting in the stretching vibration of –NH and –CH group of DMAP+ towards the lower wavenumber side. To explore the significance of hydrogen bonding, quantum theory of atoms in molecules (QTAIM) has been employed, and the findings suggest that the N23–H24⋅⋅⋅N9 bond is a strong intermolecular hydrogen bond. The decrement in the HOMO-LUMO gap, which is calculated from NF → NF-DMAP, reveals that the active pharmaceutical ingredient is chemically less reactive compared to the salt. The electrophilicity index (ω) profiles for NF and DMAP confirms that NF is acting as electron acceptor while DMAP acts as electron donor. The reactive sites of the salt are plotted by molecular electrostatic potential (MEP) surface and calculated using local reactivity descriptors. / SERB, DST, India, for providing the National Post-doctoral Fellowship (Project File Number: PDF/2016/003162); Central Facility for Computational Research (CFCR), University of Lucknow; Newton-Bhabha Ph.D. placement award (2017); Royal Society seed corn research grant (2018-19)

Yes / The creation of co-crystals as a route to creating new pharmaceutical phases with modified or defined physicochemical properties is an area of intense research. Much of the current research has focused on creating new phases for numerous active pharmaceutical ingredients (APIs) to alter physical properties such as low solubilities, enhancing processability or stability. Such studies have identified suitable co-formers and common bonding motifs to aid with the design of new co-crystals but understanding how the changes in the molecular structure of the components are reflected in the packing and resulting properties is still lacking. This lack of insight means that the design and growth of new co-crystals is still a largely empirical process with co-formers selected and then attempts to grow the different materials undertaken to evaluate the resulting properties. This work will report on the results of a combination of crystal structure database analysis with computational chemistry studies to identify what structural features are retained across a selection of families of co-crystals with common components. The competition between different potential hydrogen bonding motifs was evaluated using ab initio quantum mechanical calculations and this was related to the commonality in the packing motifs when observed. It is found while the stronger local bonding motifs are often retained within systems, the balance of weaker long-range packing forces gives rise to many subtle shifts in packing leading to greater challenges in the prediction of final crystal structures.

Understanding the Earth’s interior requires exploring minerals under extreme pressures and temperatures, conditions often unattainable by experimental methods. Atomistic simulations provide a powerful tool to investigate these extreme environments, offering insights into minerals' physical and chemical behavior deep within the Earth. However, complex phase relations and pronounced anharmonic effects pose significant challenges to these simulations. To address these challenges, we developed advanced methodologies and employed cutting-edge atomistic simulation techniques. Our work focused on modeling phonon behavior, simulating X-ray, IR, and Raman spectroscopy, and evaluating key properties such as thermodynamics, compressive strength, and thermoelasticity. We extended the quasiharmonic approximation for thermoelasticity and introduced a new formalism for third-order elasticity to tackle the complexities inherent in these systems. Our research sheds light on phenomena like hydrogen bond disordering, tunneling, diffusion, and hydrogen bond-induced elastic anisotropy under extreme pressure. These advancements significantly enhance our understanding of the thermal and chemical structures of the Earth’s deep interior.

Les dérivés cyclopropanoïques sont des composés importants dans plusieurs domaines tels que la synthèse organique, la chimie médicinale et la science des matériaux. La synthèse asymétrique des dérivés cyclopropanoïques s'est de plus en plus concentrée sur la synthèse stéréocontrolée de cyclopropanes polysubstitutés qui arborent toute une gamme de substituants distincts. Ces méthodes permettent d’accéder à des synthèses divergentes pour préparer des composés pharmaceutiques comportant cette sous-unité. De plus, l'ouverture facile de ce cycle très tendu en fait une bonne cible pour étudier l'activation de la liaison C‒C. C’est pourquoi les cyclopropanes sont parmi les composés les plus attrayants et les plus diversifiés en synthèse organique. La synthèse divergente de dérivés cyclopropanoïques repose sur l'utilisation de précurseurs stables mais réactifs. L'une des réactions pour former des liaisons C‒C les plus couramment utilisées dans la fonctionnalisation à un stade avancé, est la réaction de couplage croisé de Suzuki-Miyaura. C'est l'une des raisons pour lesquelles les borocyclopropanes sont devenus des précurseurs synthétiques attrayants pour la fonctionnalisation et diversification des molécules complexes. L’accès à de telles molécules faciliterait la préparation de molécules cyclopropanoïques de structures diversifiées. Il est difficile de préparer des borocyclopropanes de manière énantiosélective. Dans cette thèse, une cyclopropanation énantiosélective d'acides boroniques protégés dérivés d'alcools allyliques a été réalisée via la réaction de cyclopropanation asymétrique en présence du ligand chiral de type dioxaborolane. Le développement de cette méthodologie a nécessité une modification de la décomplexation oxydative existante du dioxaborolane via son complexe dérivé de la diéthanolamine. Le protocole est maintenant applicable aux dérivés boronates qui incluent des groupements fonctionnels qui sont incompatibles avec les bases. Les borocyclopropanes tétracoordonnés obtenus permettent également la formation de liaisons C‒C et ont démontré une stabilité améliorée par rapport à leurs dérivés tricoordonnés. Une étude plus approfondie sur des complexes cyclopropylméthylamine-boranes (CAB) a démontré que ces derniers pouvaient conduire aux amine-boranes spirocycliques (SCAB). Ces SCAB ont été obtenus grâce à une cascade d'activation des CABs en utilisant le bis(trifluorométhanesulfonimide) (Tf2NH) comme initiateur. L'ouverture du cycle des CAB représente la première conversion des cyclopropanes en spirocycles contenant à la fois un N-spirocentre et un spiro amine-borane. Les amine-boranes ont démontré une activité pharmacologique telle que des propriétés anticancéreuses, anti-inflammatoires et anti-ostéoporotiques. L'incorporation de spirocycles dans un motif augmente le caractère sp3 et la chiralité inhérente. Les SCAB rendent alors des candidats attrayants pour la conception de médicaments. La réaction de SCAB avec de Tf2NH en quantités stoechiométriques a donné un complexe SCAB•NTf2 qui est capable de réduire les fonctions cétone, aldéhyde, imine, nitrobenzène, nitrosobenzène, anthracène, indole et aryl méthyl éther. Le complexe SCAB•NTf2 est également capable de réduire le diphénylacétylène de manière Z-sélective en cis-stilbène. Des études spectroscopiques approfondies ont donné plus d'informations sur la structure de SCAB•NTf2 et nous ont permis de proposer un mécanisme de réduction des groupements fonctionnels ci-dessus. Les études spectroscopiques (RMN, IR et Raman) ont également révélé l'implication d'une liaison α-C‒H au bore dans une liaison hydrogène hypsochromique « improper hydrogen bond » avec [Tf2N]-. L'hyperconjugaison avec l’atome de bore, un acide de Lewis, est proposée, ce qui rend la liaison C‒H acide et donc suffisamment polarisée pour agir comme un donneur de pont hydrogène. / Cyclopropane derivatives are incredibly versatile building blocks used in organic synthesis, medicinal chemistry, and materials science. The asymmetric synthesis of cyclopropane derivatives has increasingly focused on achieving polysubstituted cyclopropanes with a range of distinct substituents and their use in divergent syntheses to access pharmaceutical compounds. Moreover, the ring-opening potential of the cyclopropane ring, due to its inherent strain, makes it a facile target for C‒C bond activation and one of the most attractive and diverse cycloalkanes in organic synthesis. Divergent synthesis of cyclopropanes relies on stable pre-installed handles on cyclopropanes that can be activated readily. One of the most common C‒C bond formation approaches used in late-stage functionalization is the Suzuki-Miyaura cross-coupling reaction. As a result, borocyclopropanes have become attractive synthetic building blocks for their use in late-stage functionalization. Methods for the enantioselective synthesis of borocyclopropanes are scarce. In this thesis, the first enantioselective cyclopropanation of an allylic alcohol bearing a tetracoordinate boronate has been achieved via the Charette dioxaborolane-mediated enantioselective cyclopropanation reaction. The development of our method required modification of the existing oxidative decomplexation of dioxaborolane via diethanolamine. The protocol has now been expanded to include boronates and base-sensitive functionalities. The tetracoordinate borocyclopropane obtained was also shown to undergo C‒C bond formation and demonstrated enhanced stability compared to its tricoordinate boronate derivative. Further investigation of boron tethered cyclopropanes led to the discovery of the unique transformation of cyclopropane amine-boranes (CABs) to spirocyclic amine-boranes (SCABs). SCABs were obtained through a cascade activation of CAB via bis(trifluoromethane)sulfonimide (Tf2NH). The ring-opening of CABs represents the first conversion of cyclopropanes to spirocycles containing an N-spirocenter and furthermore an amine-borane spirocore. Amine-boranes have shown pharmacological activity such as anti-cancer, anti-inflammatory, and anti-osteoporotic properties. Incorporating spirocycles into a motif increases sp3 character and inherent chirality, rendering SCABs as attractive candidates for drug design. The reaction of SCAB with stoichiometric amounts of Tf2NH resulted in a SCAB•NTf2 complex that was found to be able to reduce ketone, aldehyde, imine, nitrobenzene, nitrosobenzene, anthracene, and indole functionalities as well as demethylate aryl methyl ethers. The SCAB•NTf2 complex was also capable of reducing diphenylacetylene in a Z-selective manner to cis-stilbene. In-depth spectroscopic studies revealed the structure of SCAB•NTf2 and a mechanism for the reduction of the above functionalities is proposed. The spectroscopic studies (NMR, IR and Raman) revealed the involvement of an α-C‒H bond to boron in improper hydrogen bonding with [Tf2N]-. Hyperconjugation to the Lewis acidic boron is proposed to make the C‒H bond acidic and therefore polarized enough to act as a hydrogen bond donor.

<p>The structure, bonding and chemistry of water and hydroxyl on metal surfaces are presented. Synchrotron based x-ray photoelectron- and x-ray absorption spectroscopy along with density functional theory calculations mainly form the basis of the results. Conditions span the temperature range 35 - 520 K and pressures from ultra-high vacuum (~10 fAtm) to near ambient pressures (~1 mAtm). The results provide, e.g, new insights on the importance of hydrogen bonding for surface chemical kinetics.</p><p>Water adsorbs intact on the Pt(111), Ru(001) and Cu(110) surfaces at low temperatures forming 2-dimensional wetting layers where bonding to the metal (M) mainly occurs via H₂O-M and M-HOH bonds. Observed isotope differences in structure and kinetics for H₂O and D₂O adsorption on Ru(001) are due to qualitatively different surface chemistries. D₂O desorbs intact but H₂O dissociates in kinetic competition with desorption similar to the D₂O/Cu(110) system. The intact water layers are very sensitive to x-ray and electron induced damage.</p><p>The mixed H₂O:OH phase on Ru(001) consists of stripe-like structures 4 to 6 Ru lattice parameters wide where OH decorates the edges of the stripes. On Pt(111), two different long-range ordered mixed H₂O:OH structures are found to be inter-related by geometric distortions originating from the asymmetric H-bond donor-acceptor properties of OH towards H₂O.</p><p>Water adsorption on Cu(110) was studied at near ambient conditions and compared to Cu(111). Whereas Cu(111) remains clean, Cu(110) holds significant amounts of water in a mixed H₂O:OH layer. The difference is explained by the differing activation barriers for water dissociation, leading to the presence of OH groups on Cu(110) which lowers the desorption kinetics of water by orders of magnitude due to the formation of strong H₂O-OH bonds. By lowering the activation barrier for water dissociation on Cu(111) by pre-adsorbing atomic O, generating adsorbed OH, similar results to those on Cu(110) are obtained.</p>

This thesis presents the results and discussion of the investigation of the effects of Brönsted bases on the kinetics and thermodynamics of two proton-coupled electron transfer processes: the mediated oxidation of glutathione and the electrochemical oxidation of hydroquinone. Proton-coupled electron transfer (PCET) is the name given to reactions that involve the transfer of electron(s) accompanied by the exchange of proton(s). PCETs are found in many chemical and biological processes, some of current technological relevance such as the oxygen reduction reaction in fuel cells, which involves the transfer of four electrons and four protons (4e-, 4H+); or the splitting of water into protons (4H+), electrons (4e-) and oxygen (O2) efficiently achieved in photosynthesis. The study of PCET mechanisms is imperative to understanding biological processes as well as to developing more efficient technological applications. However, there are still many unanswered questions regarding the kinetic and thermodynamic performance of PCETs, and especially about the effect of different proton acceptors on the rate and mechanism of PCET reactions. This study aimed to investigate the effect of Brönsted bases as proton acceptors on the kinetics and thermodynamics of two model PCET processes, the oxidation of glutathione and hydroquinone. The analysis presented in this thesis provides insight into the influence of different proton acceptors on the mechanism of PCET and it does so by studying these reactions from a different angle, that one of the acid-base catalysis theory which has been successfully applied to the investigation of numerous chemical reactions coupled to proton transfer. We hope future research of PCETs can benefit from the knowledge of acid-base catalysis to better understand these reactions at a molecular level.